The objective of this doctoral thesis is to develop the knowledge on optimization in colon neoplasias detection strategies. The findings of the studies offer an important contribution to the knowledge in the field of the colorectal cancer screening.
The thesis consists of two separate projects. The first of them is focused on the fecal immunochemical test (FIT) and its objective is to evaluate its performance at different positivity cut-off values in a population-based colorectal cancer screening program, stratified by age and sex. This study shows that FIT cut-off values could be individualized by age and gender to improve the performance of the test in CRC screening programs. The study gives useful information to optimize resources and to plan a screening program. The second project is focused on colonoscopy, and it analyses the prevalence of serrated polyps and its relationship with synchronous advanced neoplasia. This study shows that large serrated polyps have low prevalence in average-risk individuals and, independently of their proximal or distal location, they are associated with the presence of synchronous advanced neoplasia. Advanced neoplasm associated risk is of the same magnitude to the risk of having three or more small tubular adenomas. This reinforces the recommendation of surveillance after three years. Furthermore, proximal hyperplastic polyps are related to the presence of synchronous advanced neoplasia, although further studies are needed to determine definitely the risk of patients with proximal hyperplastic polyps. These results emphasize the importance of endoscopic detection of these lesions with high quality screening examination.
Both projects are based on the COLONPREV study, a population-based, multicenter, nationwide, randomized controlled trial designed to compare the efficacy of one-time colonoscopy and biennial FIT in reducing CRC-related mortality. The strength of both projects is that they are based on a recent, large, nationwide, controlled randomized and multicenter trial, which ensures the reliability of the data.
On the other hand, the projects have some limitations as well. In the first project, results were analysed based on one FIT screening round, which does not reflect real world practice, in which people urdergo repeated testing. Prospective studies conducted over consecutive rounds are needed to determine if results are altered. Another limitation is that the study was performed in one country only, and that other factors such as smoking status, or body mass index were not evaluated and could have an influence on the results. Finally, test sensitivity and specificity could not be determined because only FIT positive individuals underwent colonoscopy. The second project also has some limitations, the most important being that pathologic criteria for the diagnosis of serrated polyps were not centrally reviewed. Interobserver variation among pathologists could have therefore influenced the results. Other limitations are that the relationship between each type of non-hyperplastic serrated polyp could not be determined, and that the relationship between large serrated polyps and CRC could not be established due to the few cases of diagnosed CRC.
Both projects have been published in indexed journals with a total impact factor of 8.332, and this thesis is presented as compendium of both publications.
Finally, this thesis opens the door to future research projects, both in the area of average-risk individuals that undergo colorectal cancer screening and in the surveillance of CRC screening diagnosed lesions.